The Mechanism of Action of Lysobactin.
The Mechanism of Action of Lysobactin.
复制标题
溶酶体的作用机理。
DOI：
10.1021/jacs.5b11807
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发表时间：
2016-01-13
影响因子：
15
通讯作者：
Walker S
中科院分区：
文献类型：
--
作者：
Lee W;Schaefer K;Qiao Y;Srisuknimit V;Steinmetz H;Müller R;Kahne D;Walker S
溶菌素，也被称为katanosin B，是一种有效的抗生素，在体内对金黄色葡萄球菌和肺炎链球菌有效。其抑制肽聚糖（PG）生物合成的作用已被证实，但其分子机制尚未确定。通过酶抑制实验，我们发现溶菌素与脂质I、脂质II和底物在PG和壁苔藻酸（WTA）生物合成途径中形成1:1的复合物。因此，溶索巴actin，像ramoplanin和teixobactin一样，识别脂质连接细胞壁前体的还原端。我们表明，尽管溶菌素能够结合来自不同途径的前体，但溶菌素的细胞杀伤机制完全是由于脂质II结合，这导致间隔缺陷和灾难性的细胞包膜损伤。
Lysobactin, also known as katanosin B, is a potent antibiotic with in vivo efficacy against Staphylococcus aureus and Streptococcus pneumoniae. It was previously shown to inhibit peptidoglycan (PG) biosynthesis, but its molecular mechanism of action has not been established. Using enzyme inhibition assays, we show that lysobactin forms 1:1 complexes with Lipid I, Lipid II, and , substrates in the PG and wall teichoic acid (WTA) biosynthetic pathways. Therefore, lysobactin, like ramoplanin and teixobactin, recognizes the reducing end of lipid-linked cell wall precursors. We show that despite its ability to bind precursors from different pathways, lysobactin’s cellular mechanism of killing is due exclusively to Lipid II binding, which causes septal defects and catastrophic cell envelope damage.